Kojima T, Hayashi S, Yokoyama I, Takagi H
Department of Surgery II, Nagoya University, School of Medicine, Japan.
Transplantation. 1996 Sep 15;62(5):559-62. doi: 10.1097/00007890-199609150-00003.
It has been shown that a high dose administration of human intravenous immunoglobulin G (IVIG) prolonged the survival time of xenografted guinea pig heart in the rat. In this study, we compared the effectiveness of intact IVIG (I-IVIG), Fc fragments of IVIG (Fc-IVIG), and F(ab') fragments of IVIG (Fab-IVIG) in preventing xenogenic hyperacute rejection in the guinea pig-to-rat heart transplantation model. Relatively high dose administration of IVIG (0.6 g/kg body weight) induced xenograft survival times of 32.0 +/- 13.0 min and 33.2 +/- 16.8 min with I-IVIG and Fab-IVIG, respectively, which were significantly longer than times for animals treated with Fc-IVIG or for untreated control animals (survival times of 12.6 +/- 7.4 min and 10.4 +/- 7.6 min, respectively). The in vitro inhibitory effect of guinea pig red blood cell hemolysis by fresh rat serum correlated with the results of in vivo study. On the other hand, the in vitro inhibitory effect of IVIG on pig red blood cell hemolysis by fresh human serum showed that Fc-IVIG, which had little effect in the guinea pit-to-rat combination, had a higher inhibitory effect than Fab-IVIG, or I-IVIG. Fc-IVIG and I-IVIG achieved a complete inhibition of in vitro hemolysis in the pig-to-human combination. It is suspected that an interference with the complement classical pathway by the Fc portion of IVIG could be an attractive tool for inhibition of hyperacute rejection in the pig-to-human combination.
研究表明，大剂量静脉注射人免疫球蛋白G（IVIG）可延长异种移植到大鼠体内的豚鼠心脏的存活时间。在本研究中，我们比较了完整IVIG（I-IVIG）、IVIG的Fc片段（Fc-IVIG）和IVIG的F(ab')片段（Fab-IVIG）在豚鼠-大鼠心脏移植模型中预防异种超急性排斥反应的效果。相对高剂量的IVIG（0.6 g/kg体重）分别使用I-IVIG和Fab-IVIG时，诱导异种移植物存活时间为32.0±13.0分钟和33.2±16.8分钟，这明显长于用Fc-IVIG治疗的动物或未治疗的对照动物的存活时间（分别为12.6±7.4分钟和10.4±7.6分钟）。新鲜大鼠血清对豚鼠红细胞溶血的体外抑制作用与体内研究结果相关。另一方面，IVIG对新鲜人血清引起的猪红细胞溶血的体外抑制作用表明，在豚鼠-大鼠组合中作用较小的Fc-IVIG比Fab-IVIG或I-IVIG具有更高的抑制作用。Fc-IVIG和I-IVIG在猪-人组合中实现了对体外溶血的完全抑制。据推测，IVIG的Fc部分对补体经典途径的干扰可能是抑制猪-人组合中超急性排斥反应的一种有吸引力的工具。
